The action of radiation, chemotherapeutic drugs and other chemicals on mammalian spermatogenic cells could result in mutations or sterility. Mutations are a result of alterations in the DNA of the testis cells. We propose to examine the chemical lesions produced by these agents in testicular cells at different stages of maturation. To this end, we have developed methods for separating these cells and their nuclei. In addition we have applied flow microfluorimetric methods to the analysis of the DNA content of individual testicular cells. We have been able to detect a greater variation in DNA content between post-meiotic cells which, for genetic reasons, show irregular meiotic segregation. We intend to apply these methods to drug-treated mice. The effects of radiation and drugs on testicular stem cells and differentiated spermatogonia are being studied. The regeneration of the numbers of testicular stem cells after irradiation appear to be extremely slow. The relationship between stem cell survival or regeneration, and fertility will be analyzed. BIBLIOGRAPHIC REFERENCES: Meistrich, M.L., Reid, B.O., and Barcellona, W.J., 1975. "Meiotic DNA Synthesis During Mouse Spermatogenesis." Journal of Cell Biology 64:211. Meistrich, M.L., and Trostle, P.K., 1975. "Separation of Mouse Testis Cells by Equilibrium Density Centrifugation in Renografin Gradients." Experimental Cell Research 92:231.